title: A novel one-pot synthesis and preliminary biological activity evaluation of cis-restricted polyhydroxy stilbenes incorporating protocatechuic acid and cinnamic acid fragments.
abstract: A series of new stilbenes 4a-e, 5 were synthesized through a novel one-pot Perkin-like reaction between 6,7-dimethoxyhomophthalic anhydride and aromatic aldehydes, followed by treatment with BBr3. This synthesis is straightforward and allows polyhydroxylated cis-stilbenes gathering two well-known pharmacophoric fragments to be obtained in good yields and for short reaction times. The structure of the newly synthesized compounds was established by spectroscopic methods ((1)H NMR, (13)C NMR, IR and HRMS) and the double bond configuration was unequivocally elucidated by means of gated decoupling (13)C NMR spectra and 2D NOESY experiments. Preliminary differentiating screening of their radical scavenging, antibacterial, anti-fungal and tyrosinase inhibitory activity was further performed. The results obtained suggest that the tested compounds possess a triple biological action as potent radical scavengers, antifungal agents and tyrosinase inhibitors in micromolar concentration. The most promising bioactive compound amongst the others was 4a, acting as excellent radical scavenger against DPPH(•) radical (IC₅₀ ≤ 10 μM), antifungal agent suppressing the growth of Fusarium graminearum (89% inhibition at 0.17 μmol/mL), and tyrosinase inhibitor showing higher activity than hydroquinone at 23 μM.
authors.affiliation: Faculty of Chemistry and Pharmacy, University of Sofia St. Kl. Ohridski, 1, James Bourchier Blvd., 1164 Sofia, Bulgaria.
authors.forename: Mitko
authors.initials: M
authors.lastname: Miliovsky
authors.forename: Ivan
authors.initials: I
authors.lastname: Svinyarov
authors.forename: Yavor
authors.initials: Y
authors.lastname: Mitrev
authors.forename: Yana
authors.initials: Y
authors.lastname: Evstatieva
authors.forename: Dilyana
authors.initials: D
authors.lastname: Nikolova
authors.forename: Maya
authors.initials: M
authors.lastname: Chochkova
authors.forename: Milen G
authors.initials: MG
authors.lastname: Bogdanov
mesh_terms: D000363:Agaricales / Q000201:enzymology; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D002934:Cinnamates / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects; D062385:Hydroxybenzoates / Q000737:chemistry*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000890:Anti-Infective Agents; D002934:Cinnamates; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D062385:Hydroxybenzoates; D013267:Stilbenes; C029010:cinnamic acid; C009091:protocatechuic acid; D014442:Monophenol Monooxygenase
keywords: AATKSLBQUSPGJS-UHFFFAOYSA-N; Antifungal activity; Antioxidant activity; Homophthalic anhydride; Polyhydroxy stilbenes; RGQGZYMZKLUPJT-VGOFMYFVSA-N; Tyrosinase inhibitors; ULJDJCKWWIKHIA-IZZDOVSWSA-N; VHQOVRDJQOKEHD-UNXLUWIOSA-N; XMTFFGGKUJWXQG-CXUHLZMHSA-N; YJOUNFAKLPBLDQ-VZUCSPMQSA-N; YTBJBAKVIKEZBR-YCRREMRBSA-N